tbuckley/cabot-search huggingface dataset:
Functional, structural, and molecular characterizations of the leukemogenic driver MEF2D-HNRNPUL1 fusion
Authors: Ming Zhang, Hao Zhang, Zhihui Li, Ling Bai, Qianqian Wang, Jianfeng Li, Minghao Jiang, Qing Xue, Nuo Cheng, Weina Zhang, Dongdong Mao, Zhiming Chen, Jinyan Huang, Guoyu Meng, Zhu Chen, Sai-Juan Chen
Journal: Blood (2022)

Recurrent MEF2D fusions with poor prognosis have been identified in B-cell precursor ALL (BCP-ALL). The molecular mechanisms underlying the pathogenic function of MEF2D fusions are poorly understood. Here, we show that MEF2D-HNRNPUL1 (MH) knock-in mice developed a progressive disease from impaired B-cell development at the pre-pro-B stage to pre-leukemia over 10 to 12 months. When cooperating with NRASG12D, MH drove an outbreak of BCP-ALL, with a more aggressive phenotype than the NRASG12D-induced leukemia. RNA-sequencing identified key networks involved in disease mechanisms. In chromatin immunoprecipitation-sequencing experiments, MH acquired increased chromatin-binding ability, mostly through MEF2D-responsive element (MRE) motifs in target genes, compared with wild-type MEF2D. Using X-ray crystallography, the MEF2D-MRE complex was characterized in atomic resolution, whereas disrupting the MH-DNA interaction alleviated the aberrant target gene expression and the B-cell differentiation arrest. The C-terminal moiety (HNRNPUL1 part) of MH was proven to contribute to the fusion protein's trans-regulatory activity, cofactor recruitment, and homodimerization. Furthermore, targeting MH-driven transactivation of the HDAC family by using the histone deacetylase inhibitor panobinostat in combination with chemotherapy improved the overall survival of MH/NRASG12D BCP-ALL mice. Altogether, these results not only highlight MH as an important driver in leukemogenesis but also provoke targeted intervention against BCP-ALL with MEF2D fusions.
Practical consequences of flawed social psychological research on bias
Authors: Hal R. Arkes
Journal: Behavioral and Brain Sciences (2022)

Abstract The flaws in social psychological research pointed out by Cesario have societal costs. These include ignoring crucial base rates thereby degrading the effectiveness of policy decisions, generalizing the conclusions derived from experiments on non-professionals thereby distorting the public's view of professional law enforcement personnel, questionable accusations of racism, and mis-attributions of the causes of racial differences in behavior.
Prostate Cancer With Solitary Bone Metastasis in the Mandible
Authors: Yang Lu
Journal: Clinical Nuclear Medicine (2022)

A 79-year-old man with prostate cancer found to have a solitary bone lesion in the mandible on initial staging bone scan. The sclerotic lesion had a sunburst appearance on CT. As biopsy was nondiagnostic, the patient underwent segmental mandibulectomy. Postoperative pathology results confirmed as metastasis from prostate cancer.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Essential Serine SynthesisPhosphoglycerate dehydrogenase (PHGDH) is the first enzyme in the cascade leading to serine synthesis from glucose within the cell.This study from D'Avola and colleagues examined PHGDH and other serine synthesis components within the germinal center, a structure where B cells are activated to drive antibody-based responses to infection and to generate immune memory.Following discovery via scRNA-seq, the authors used flow cytometry, immunostaining, and labeled carbon assays to demonstrate that high expression and activity of these enzymes is specific to cycling (i.e., activated) B cells.Knockout or inhibition of PHGDH in human cells and mouse models results in impaired antibody production and immune response, as well as induction of apoptosis in lymphomas derived from this compartment.Expert Commentary: The finding that PHGDH inhibition is apoptosisinducing in lymphoma cells, but only cytostatic in normal B cells suggests that such inhibition could enable lymphoma treatment while preserving some of the host immune response.
Errors in Table
Journal: JAMA Network Open (2022)

Preceding Mass PublicShootings in the United States, 1966 to 2019," 1 published November 4, 2021, there were errors in Table 3.The odds ratios that appear in model 3 for psychiatric medication, social media use, planning, performance, interest in past mass violence, and fame-seeking motive should have read NA, 1.7 (0.4-7.6), 3.1 (0.9-11.0), 1.3 (0.2-8.3), 2.0 (0.5-7.6), and 0.3 (0.0-2.4), respectively.The P values should have read NA, .46,.08,.77,.29. and .25,respectively.This article has been corrected.
Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion
Authors: Byong-Sop Song, Ji Sun Moon, Jingwen Tian, Ho Yeop Lee, Byeong Chang Sim, Seok-Hwan Kim, Seul Gi Kang, Jung Tae Kim, Ha Thi Nga, Rui Benfeitas, Yeongmin Kim, Sanghee Park, Robert R. Wolfe, Hyuk Soo Eun, Minho Shong, Sunjae Lee, Il-Young Kim, Hyon-Seung Yi
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Mitochondria are involved in cancer energy metabolism, although the mechanisms underlying the involvement of mitoribosomal dysfunction in hepatocellular carcinoma (HCC) remain poorly understood. Here, we investigated the effects of mitoribosomal impairment-mediated alterations on the immunometabolic characteristics of liver cancer. Methods We used a mouse model of HCC, liver tissues from patients with HCC, and datasets from The Cancer Genome Atlas (TCGA) to elucidate the relationship between mitoribosomal proteins (MRPs) and HCC. In a mouse model, we selectively disrupted expression of the mitochondrial ribosomal protein CR6-interacting factor 1 (CRIF1) in hepatocytes to determine the impact of hepatocyte-specific impairment of mitoribosomal function on liver cancer progression. The metabolism and immunophenotype of liver cancer was assessed by glucose flux assays and flow cytometry, respectively. Results Single-cell RNA-seq analysis of tumor tissue and TCGA HCC transcriptome analysis identified mitochondrial defects associated with high-MRP expression and poor survival outcomes. In the mouse model, hepatocyte-specific disruption of the mitochondrial ribosomal protein CRIF1 revealed the impact of mitoribosomal dysfunction on liver cancer progression. Crif1 deficiency promoted programmed cell death protein 1 expression by immune cells in the hepatic tumor microenvironment. A [U- 13 C 6 ]-glucose tracer demonstrated enhanced glucose entry into the tricarboxylic acid cycle and lactate production in mice with mitoribosomal defects during cancer progression. Mice with hepatic mitoribosomal defects also exhibited enhanced progression of liver cancer accompanied by highly exhausted tumor-infiltrating T cells. Crif1 deficiency induced an environment unfavorable to T cells, leading to exhaustion of T cells via elevation of reactive oxygen species and lactate production. Conclusions Hepatic mitoribosomal defects promote glucose partitioning toward glycolytic flux and lactate synthesis, leading to T cell exhaustion and cancer progression. Overall, the results suggest a distinct role for mitoribosomes in regulating the immunometabolic microenvironment during HCC progression.
High prevalence of Pseudomonas aeruginosa carriage in residents of French and German long-term care facilities
Authors: Daniel Martak, Houssein Gbaguidi-Haore, Alexandre Meunier, Benoit Valot, Nadine Conzelmann, Michael Eib, Ingo B. Autenrieth, Céline Slekovec, Evelina Tacconelli, Xavier Bertrand, Silke Peter, Didier Hocquet, Julia Guther
Journal: Clinical Microbiology and Infection (2022)

To determine prevalence, incidence, and factors associated with Pseudomonas aeruginosa (PA) intestinal carriage in residents of long-term care facilities (LTCFs) and to understand the population structure of this pathogen in LTCFs from two European countries.We assessed the prevalence of PA intestinal carriage and the incidence of acquisition by collecting fecal samples from 403 residents of 20 LTCFs. We collected 289 environmental samples from sinks and drinking water. Factors associated with carriage and acquisition of intestinal PA were identified. All PA isolates had their antibiotic phenotypic resistance profile determined and their genome sequenced, from which we assessed the population structure of the collection and identified resistance determinants.We found a high proportion of residents with PA intestinal carriage (51.6%) over the entire study period. Over the follow-up period, 28.6% of the residents acquired intestinal PA. Older age (OR, 1.29; 95% CI, 1.09-1.52; p = 0.002), urinary incontinence (OR, 2.56; 95% CI, 1.37-4.88; p = 0.003), and male sex (OR, 2.55; 95% CI, 1.05-6.18; p = 0.039) were associated with higher probability of carriage. Wheelchair usage (OR, 4.56; 95% CI, 1.38-15.05; p = 0.013) and a body mass index >25 (OR, 3.71; 95% CI, 1.17-11.82; p = 0.026) were associated with higher risk of PA acquisition. Population structure of our isolates was mainly non-clonal with 112 different STs among the 241 isolates. Most represented STs were high risk clones ST253 (n = 26), ST17 (n = 11), ST244 (n = 11), ST309 (n = 10), and ST395 (n = 10). Most PA isolates (86.3%) were susceptible to antibiotics, with no acquired genes conferring resistance to antipseudomonal agents.We found an unexpected high prevalence of PA intestinal carriage in LTCF residents mainly associated with individual-level factors. Our study revealed a polyclonal PA population structure suggesting that individual acquisition is more frequent than resident-to-resident transmission.
Clinical severity of COVID-19 in patients admitted to hospital during the omicron wave in South Africa: a retrospective observational study
Authors: Waasila Jassat, Salim S Abdool Karim, Caroline Mudara, Richard Welch, Lovelyn Ozougwu, Michelle J Groome, Nevashan Govender, Anne von Gottberg, Nicole Wolter, Milani Wolmarans, Petro Rousseau, Lucille Blumberg, Cheryl Cohen
Journal: The Lancet Global Health (2022)
Matrix reboot: IL-17 signals CAFs to create a second tumor T cell checkpoint
Authors: Mandy J. McGeachy
Journal: The Journal of Experimental Medicine (2022)

Excessive collagen deposition by fibroblasts surrounding some tumors has seriously limited the efficacy of checkpoint inhibitor therapies. Chen et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20210693) show that IL-17 promotes collagen deposition by cancer-associated fibroblasts, enhancing immune exclusion of tumors, and that targeting IL-17–triggered HIF1α expression can reverse matrix mediated immune exclusion.
Assessment of donor cell engraftment after hematopoietic stem cell transplantation for sickle cell disease: A review of current and future methods
Authors: Jasmine Lewis, Steven C. Greenway, Faisal Khan, Gurpreet Singh, Monica Bhatia, Gregory M. T. Guilcher
Journal: American Journal of Hematology (2022)

Hematopoietic stem cell transplantation (HSCT) is the only established curative treatment for sickle cell disease (SCD), a debilitating red blood cell (RBC) disorder with significant prevalence worldwide. Accurate assessment of RBC engraftment following HSCT is essential to evaluate the status of the graft and can enable early intervention to treat or prevent graft rejection. Currently, chimerism measurement is performed on whole blood samples, which mainly reflect white blood cell (WBC) chimerism. This approach has limitations in assessing engraftment in patients with SCD because RBCs engraft non-linearly with WBCs. Direct measures of RBC chimerism exist but are not routinely used. In this review, we critically examine the current methodologies for assessing donor engraftment; highlight the limitations of these different methods, and present emerging and novel technologies with the potential to improve clinical monitoring of RBC engraftment post-HSCT for SCD. Promising alternative methodologies include RBC-specific flow cytometry, RBC-specific RNA analysis, and quantification of plasma cell-free DNA derived specifically from nucleated RBCs.
Infrequent Intranasal Oxytocin Followed by Positive Social Interaction Improves Symptoms in Autistic Children: A Pilot Randomized Clinical Trial
Authors: Jiao Le, Lan Zhang, Weihua Zhao, Siyu Zhu, Chunmei Lan, Juan Kou, Qianqian Zhang, Yingying Zhang, Qin Li, Zhuo Chen, Meina Fu, Christian Montag, Rong Zhang, Wenxu Yang, Benjamin Becker, Keith M. Kendrick
Journal: Psychotherapy and Psychosomatics (2022)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; There are currently no approved drug interventions for social behavior dysfunction in autism spectrum disorder (ASD). Previous trials investigating effects of daily intranasal oxytocin treatment have reported inconsistent results and have not combined it with positive social interaction. However, in two preclinical studies we established that treatment every other day rather than daily is more efficacious in maintaining neural and behavioral effects by reducing receptor desensitization. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; We aimed to establish whether a 6-week intranasal oxytocin compared with placebo treatment, followed by a period of positive social interaction, would produce reliable symptom improvements in children with ASD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A pilot double-blind, randomized, crossover design trial was completed including 41 children with ASD aged 3–8 years. Primary outcomes were the Autism Diagnostic Observation Schedule-2 (ADOS-2) and social responsivity scale-2 (SRS-2). Secondary measures included cognitive, autism- and caregiver-related questionnaires, and social attention assessed using eye-tracking. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Significant improvements were found for oxytocin relative to placebo in primary outcome measures (total ADOS-2 and SRS-2 scores, &lt;i&gt;p&lt;/i&gt;s &amp;#x3c; 0.001) and in behavioral adaptability and repetitive behavior secondary measures. Altered SRS-2 scores were associated with increased saliva oxytocin concentrations. Additionally, oxytocin significantly increased time spent viewing dynamic social compared to geometric stimuli and the eyes of angry, happy, and neutral expression faces. There were no adverse side effects of oxytocin treatment. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Overall, results demonstrate that a 6-week intranasal oxytocin treatment administered every other day and followed by positive social interactions can improve clinical, eye tracking, and questionnaire-based assessments of symptoms in young autistic children.
Prospective cardiovascular evaluation with 24-hour Holter and 24-hour ambulatory blood pressure monitoring in men using 5-mg oral minoxidil for androgenetic alopecia
Authors: Baltazar Dias Sanabria, Eduardo Palmegiani, Andressa Fernandes Seron, Yuri Chiarelli Perdomo, Hélio Amante Miot, Paulo Müller Ramos
Journal: Journal of the American Academy of Dermatology (2022)
Association of Mild Valvular Lesions With Long-term Cardiovascular Outcomes Among Black Adults
Authors: Kunihiro Matsushita, Yumin Gao, Jonathan Rubin, Ajay J. Kirtane, Susheel Kodali, Elizabeth Selvin, Alvaro Alonso, Martin B. Leon, Scott D. Solomon, Josef Coresh, Ervin R. Fox, Amil M. Shah
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Little is known about the long-term outcomes of mild valvular lesions. <h3>Objective</h3> To examine the associations of 3 major types of valvular lesions (aortic stenosis, trace or mild aortic regurgitation, and trace or mild mitral regurgitation) with risk of cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, and atrial fibrillation. <h3>Design, Setting, and Participants</h3> This cohort study analyzed data from the ongoing Atherosclerosis Risk in Communities study and focused on Black participants in the Jackson, Mississippi, site who underwent echocardiography at visit 3 from 1993 to 1995. Data analysis was conducted between April 2021 and February 2022. <h3>Exposures</h3> Three valvular lesions were analyzed: aortic sclerosis, aortic regurgitation (trace or mild), and mitral regurgitation (trace or mild). <h3>Main Outcomes and Measures</h3> The outcomes were cardiovascular mortality, coronary heart disease, heart failure, stroke, and atrial fibrillation. Multivariable Cox proportional hazards regression models were used to examine the independent associations between the 3 valvular lesions and these outcomes. <h3>Results</h3> A total of 2106 Black participants were included, with a mean (SD) age of 59.1 (5.6) years and 1354 women (64.3%). The baseline prevalence was 7.7% for aortic sclerosis, 15.1% for aortic regurgitation (6.1% with trace, and 9.0% with mild), and 43.0% for mitral regurgitation (29.4% with trace, and 13.6% with mild). During a median (interquartile interval) follow-up of 22.5 (15.6-23.5) years, 890 participants developed at least 1 cardiovascular outcome. Each valvular lesion was significantly associated with at least 1 cardiovascular outcome: aortic sclerosis was associated with cardiovascular mortality (adjusted hazard ratio [HR], 1.54; 95% CI, 1.06-2.22), mild mitral regurgitation was associated with atrial fibrillation (HR, 1.47; 95% CI, 1.09-1.99), and trace or mild aortic regurgitation was associated with all outcomes (HRs ranging from 1.45 [95% CI, 1.17-1.81] to 1.75 [95% CI, 1.29-2.37]) except stroke. The total number of valvular lesions had graded associations with all cardiovascular outcomes except stroke: the HR of cardiovascular mortality was 1.77 (95% CI, 1.18-2.65) for those with 2 to 3 lesions and was 1.44 (95% CI, 1.05-1.96) for those with 1 lesion vs no lesions. <h3>Conclusions and Relevance</h3> Results of this study indicate an association between valvular lesions, even at mild stage, and a long-term risk of cardiovascular events, suggesting the importance of recognizing and monitoring these valvular conditions.
The “Power of Zero” in Younger Patients—A Glass Half Empty or a Glass Half Full?—Reply
Authors: Martin Bødtker Mortensen
Journal: JAMA Cardiology (2022)

In Reply We thank Lopes et al for the thoughtful comments on our recent article on the diagnostic value of a coronary artery calcium (CAC) score of zero to rule out obstructive coronary artery disease (CAD) in patients with stable chest pain.1 We agree with the points made by Lopes et al.
Pannexin 1 drives efficient epithelial repair after tissue injury
Authors: Christopher D. Lucas, Christopher B. Medina, Finnius A. Bruton, David A. Dorward, Michael H. Raymond, Turan Tufan, J. Iker Etchegaray, Brady Barron, Magdalena E. M. Oremek, Sanja Arandjelovic, Emily Farber, Suna Onngut-Gumuscu, Eugene Ke, Moira K. B. Whyte, Adriano G. Rossi, Kodi S. Ravichandran
Journal: Science Immunology (2022)

Epithelial tissues such as lung and skin are exposed to the environment and therefore particularly vulnerable to damage during injury or infection. Rapid repair is therefore essential to restore function and organ homeostasis. Dysregulated epithelial tissue repair occurs in several human disease states, yet how individual cell types communicate and interact to coordinate tissue regeneration is incompletely understood. Here, we show that pannexin 1 (Panx1), a cell membrane channel activated by caspases in dying cells, drives efficient epithelial regeneration after tissue injury by regulating injury-induced epithelial proliferation. Lung airway epithelial injury promotes the Panx1-dependent release of factors including ATP, from dying epithelial cells, which regulates macrophage phenotype after injury. This process, in turn, induces a reparative response in tissue macrophages that includes the induction of the soluble mitogen amphiregulin, which promotes injury-induced epithelial proliferation. Analysis of regenerating lung epithelium identified Panx1-dependent induction of
Correspondence on Concerns About Methodology and Confounding
Authors: Renin Chang, Hui-Yuan Chen, Yao-Min Hung, James Cheng-Chung Wei
Journal: Journal of Clinical Oncology (2022)

Shen et al 1 investigated potential preventative effect of H1 antihistamine (AH) on the risk of hepatocellular carcinoma in hepatitis B virus, hepatitis C virus, and dual viral infection patients in a dose-dependent manner.
SunUp and Sunset genomes revealed impact of particle bombardment mediated transformation and domestication history in papaya
Authors: Jingjing Yue, Robert VanBuren, Juan Liu, Jingping Fang, Xingtan Zhang, Zhenyang Liao, Ching Man Wai, Xiuming Xu, Shuai Chen, Shengchen Zhang, Xiaokai Ma, Yaying Ma, Hongying Yu, Jing Lin, Ping Zhou, Yongji Huang, Ban Deng, Fang Deng, Xiaobing Zhao, Hansong Yan, Mahpara Fatima, Dessireé Zerpa-Catanho, Xiaodan Zhang, Zhicong Lin, Mei Yang, Nancy J. Chen, Eric Mora-Newcomer, Patricia Quesada-Rojas, Antonio Bogantes, Víctor M. Jiménez, Haibao Tang, Jisen Zhang, Ming-Li Wang, Robert E. Paull, Qingyi Yu, Ray Ming
Journal: Nature Genetics (2022)
ATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons
Authors: Rie Hasebe, Kaoru Murakami, Masaya Harada, Nada Halaka, Hiroshi Nakagawa, Fuminori Kawano, Yoshinobu Ohira, Tadafumi Kawamoto, Fiona E. Yull, Timothy S. Blackwell, Junko Nio-Kobayashi, Toshihiko Iwanaga, Masahiko Watanabe, Nobuhiro Watanabe, Harumi Hotta, Toshihide Yamashita, Daisuke Kamimura, Yuki Tanaka, Masaaki Murakami
Journal: The Journal of Experimental Medicine (2022)

Neural circuits between lesions are one mechanism through which local inflammation spreads to remote positions. Here, we show the inflammatory signal on one side of the joint is spread to the other side via sensory neuron–interneuron crosstalk, with ATP at the core. Surgical ablation or pharmacological inhibition of this neural pathway prevented inflammation development on the other side. Mechanistic analysis showed that ATP serves as both a neurotransmitter and an inflammation enhancer, thus acting as an intermediary between the local inflammation and neural pathway that induces inflammation on the other side. These results suggest blockade of this neural pathway, which is named the remote inflammation gateway reflex, may have therapeutic value for inflammatory diseases, particularly those, such as rheumatoid arthritis, in which inflammation spreads to remote positions.
Accuracy in social judgment does not exclude the potential for bias
Authors: Jonathan B. Freeman, Kerri L. Johnson, Steven J. Stroessner
Journal: Behavioral and Brain Sciences (2022)

Abstract Cesario claims that all bias research tells us is that people “end up using the information they have come to learn as being probabilistically accurate in their daily lives” (sect. 5, para. 4). We expose Cesario's flawed assumptions about the relationship between accuracy and bias. Through statistical simulations and empirical work, we show that even probabilistically accurate responses are regularly accompanied by bias.
Comparison of SARS-CoV-2 Antibody Response After 2-Dose mRNA-1273 vs BNT162b2 Vaccines in Incrementally Immunosuppressed Patients
Authors: Jonathan Mitchell, Caoilfhionn M. Connolly, Teresa Po-Yu Chiang, Jennifer L. Alejo, William A. Werbel, Dorry L. Segev, Allan B. Massie
Journal: JAMA Network Open (2022)